Abstract
Multiple myeloma (MM) is the second most common hematooncological disease of malignant plasma cells in the bone marrow. While new treatment brought unprecedented increase of survival of patients, MM pathogenesis is yet to be clarified. Increasing evidence of expression of long non-coding RNA molecules (lncRNA) linked to development and progression of many tumors suggested their important role in tumorigenesis. To date, over 15,000 lncRNA molecules characterized by diversity of function and specificity of cell distribution were identified in the human genome. Due to their involvement in proliferation, apoptosis, metabolism, and differentiation, they have a key role in the biological processes and pathogenesis of many diseases, including MM. This review summarizes current knowledge of non-coding RNAs (ncRNA), especially lncRNAs, and their role in MM pathogenesis. Undeniable involvement of lncRNAs in MM development suggests their potential as biomarkers.
Highlights
Multiple myeloma (MM) is the second most common hematological malignancy of plasma cells (PCs), which produce monoclonal immunoglobulin
Multiple long non-coding RNA molecules (lncRNA) expressed in various cell types bind polycomb repressive complex 2 (PRC2); small interfering RNA-mediated depletion of a number of these molecules led to enrichment of genes normally repressed by PRC2 [51]
Xue et al revealed the importance of lncRNA functional motifs in mechanisms of action, as they found out that deletion in 11 nt in an internal G-rich RNA motif (AGIL) of Bvht (Braveheart) impaired cardiomyocyte differentiation through a well-defined motif of secondary structure, regulating the cardiovascular lineage with cellular nucleic-acid-binding protein (CNBP) [60]
Summary
Multiple myeloma (MM) is the second most common hematological malignancy of plasma cells (PCs), which produce monoclonal immunoglobulin. These cells expand in the bone marrow (BM) replacing normal hematopoiesis. Genetic and epigenetic changes contribute to development of a new, aggressive clone of PCs in the BM; malignant PC accumulation can lead to the development of specific symptoms, including hypercalcemia, renal insufficiency, anemia, and osteolytic bone disease (CRAB symptoms). Long non-coding RNAs (lncRNAs) were considered to be evolutionary accumulated genetic waste until they were proven to be gene expression regulators by modern, highly sensitive genomics platforms. We review available information about lncRNAs, and their biogenesis, function, and involvement in MM pathogenesis
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